AUTHOR=Gao Shuo , Ji Yueyue , Xu Shilan , Jia Jia , Fan Baiyuan , Zhang Yan , Shen Han , Zhou Wanqing 

TITLE=Antifungal activity of nisin against clinical isolates of azole-resistant Candida tropicalis

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1383953

DOI=10.3389/fmicb.2024.1383953

ISSN=1664-302X

ABSTRACT=<p>The rapid emergence of invasive infections caused by azole-resistant <italic>Candida tropicalis</italic> has become a public health concern, and there is an urgent need for alternative treatment strategies. Studies have demonstrated the antibacterial effects of nisin, a well-known peptide naturally produced by <italic>Lactococcus lactis</italic> subsp. <italic>lactis</italic>. However, there is scant information about the antifungal effect of nisin against <italic>C. tropicalis</italic>. The present study aims to investigate the <italic>in vitro</italic> antifungal activity of nisin against clinical isolates of azole-resistant <italic>C. tropicalis</italic> strains, as well as its inhibitory effect on biofilm formation. A total of 35 <italic>C. tropicalis</italic> strains isolated from patients with invasive fungal infections were divided into the azole-resistant group and the azole-sensitive group, containing 21 and 14 strains, respectively. The relative expression levels of the <italic>ERG11</italic> and <italic>UPC2</italic> genes in the azole-resistant group were higher than those in the azole-sensitive group (<italic>p</italic> &lt; 0.0001), while no significant differences were observed in the expression levels of the <italic>MDR1</italic> and <italic>CDR1</italic> genes. The minimum inhibitory concentration of nisin against <italic>C. tropicalis</italic> ranged from 2 to 8 μg/mL. Nisin treatment inhibited the growth of azole-resistant <italic>C. tropicalis,</italic> with over a four-fold reduction in OD<sub>600 nm</sub> values observed at the 8-h time point, while it promoted the transition of <italic>C. tropicalis</italic> from the spore phase to the hyphal phase, as observed on cryo-scanning electron microscopy. The results of biofilm quantification using crystal violet staining indicated a significant decrease in OD<sub>570 nm</sub> values in the nisin-treated group compared to the controls (<italic>p</italic> &lt; 0.0001). Among the 21 azole-resistant <italic>C. tropicalis</italic> strains, the biofilm formation was inhibited in 17 strains (17/21, 81%), and more than 85% inhibition of biofilm formation was observed in the representative strains. With regard to the molecular mechanisms, the expression of the <italic>BCR1</italic> and <italic>UPC2</italic> genes in the azole-resistant strains was down-regulated on nisin treatment (<italic>p</italic> &lt; 0.05). In conclusion, we demonstrated, for the first time, that nisin has antifungal activity and significant anti-biofilm activity against clinical isolates of azole-resistant <italic>C. tropicalis</italic> strains. Based on the findings, nisin could be a promising alternative antifungal agent for combating azole-resistant <italic>C. tropicalis</italic> infections.</p>